A disorder resulting from the loss of function of neurons in the MIDBRAIN. The classic symptoms of the disease are TREMOR, muscular RIGIDITY, BRADYKINESIA and AKINESIA (respectively, slowness of and failure to initiate movement) and postural instability, including loss of coordination and a stooped posture. The affected cells are the DOPAMINE-containing cells of the SUBSTANTIA NIGRA, which form the NIGROSTRIATAL DOPAMINE SYSTEM. This projects to the dorsal STRIATUM, a major component of the BASAL GANGLIA, a group of nuclei in the basal forebrain involved in the control of movement. The disease is progressive and the cellular degeneration may begin many years before there are any symptoms. Consequently, the age of patients at the onset of the symptoms of Parkinson’s disease is typically 55 to 60 years. There is no gender bias, with equal numbers of men and women suffering from the disease, and neither are there known to be any socioeconomic or cultural effects. There is no known cause of Parkinson’s disease, hence the disease is termed IDIOPATHIC. Recent research has suggested that accumulation of FREE RADICALS within the substantia nigra might be neurotoxic (see NEUROTOXINS), though it is not clear yet whether this hypothesis will be verified (see SUPEROXIDE DISMUTASE). However, there are other forms of Parkinsonism, also resulting in loss of midbrain dopamine cells and sharing many of the symptoms, but of which the cause is known. The most well-known of these include POST-ENCEPHALITIC PARKINSONISM, in which the symptoms follow viral ENCEPHALITIS; GUAM DISEASE; and Parkinsonism resulting from MPTP toxicity.
One of the earliest symptoms of the disease is a loss of facial expression, which has been termed masked face. However, it is the tremor which usually causes the patient to seek medical attention. The characteristic features of the tremor are that it occurs at rest, when the limbs are relaxed, and there is often a rhythmic rolling of the hand, at a rate of approximately three per second, known as PILL-ROLLING. The muscular rigidity is due to non-synergistic contraction of muscles. If an attempt is made to move the patient’s limb passively, the movement will be jerky, resembling a ratchet movement and giving this feature the term COGWHEEL RIGIDITY.
The bradykinesia and akinesia render the patient unable to move freely, particularly when there is no salient stimulus to prompt the movement, and this can result in FREEZING. In more advanced and severe cases, patients may have problems walking: for example, they may be unable to initiate the next step and hence they freeze or they may fall; it has been noticed that their arms do not swing normally with their step, again leading to loss of balance and an uncoordinated gait; they may walk with a series of small, shuffling steps, which is known as FESTINATION. There are cognitive deficits also. For example, patients are impaired on tests measuring ATTENTION and the ability to plan a sequence of action. In some cases, there are also psychiatric consequences of the disease, most typically DEPRESSION but sometimes SUBCORTICAL DEMENTIA.
There is no known cure for the disease and treatments are aimed at slowing the progression of the disease and alleviating the symptoms. The most common treatment for Parkinson’s disease is the drug L-DOPA (levoDOPA), a precursor of dopamine which can increase the availability of dopamine in the brain to compensate for the reduction in dopamine due to neuronal loss. Selegiline® (DEPRENYL), chemically related to AMPHETAMINE (see PSYCHOMOTOR STIMULANTS), is a MONOAMINE OXIDASE B (MAO-B) inhibitor and is often given in conjunction with L-DOPA as it not only relieves present symptoms, but there is some indication that it also slows the progression of the disease. There are treatments, many of which are still considered experimental, which involve surgical intervention. For example, it is possible to implant dopamine-producing nerve cells, either derived from foetal brain tissue or from the patient’s own chromaffin cells of the adrenal medulla, which will secrete dopamine when in the brain (see AUTOGRAFTS; TRANSPLANTATION). There has also been a resurgence of interest in the benefits of surgical LESION of the structures on the output circuits of the basal ganglia, which are known to be overactive in the disease. By silencing these overactive cells, many of the more disabling symptoms of the disease can be ameliorated. It is also possible to silence these overactive cells by application of high-frequency stimulation: deep brain stimulation can be applied with good effect for Parkinsonism in several areas of the brain, including the GLOBUS PALLIDUS internal segment, the THALAMUS and the SUBTHALAMIC NUCLEUS. This technique also has the advantage that it is reversible (the stimulator can be turned on and off) and carries less risk of unintended damage than making a lesion. It was believed that the dopamine-containing cells were de-stroyed and that once lost, the only chance for replacement of the cells was by surgical grafting of tissue. However research suggests that, if appropriately stimulated with NERVE GROWTH FACTORS, the cells might be able to regain function.
